1. Field of the Invention
The present invention relates to a synthetic process for preparing benzo[1,2-g]-chrom-3-ene, benzo[1,2-g]-thiochrom-3-ene and benzo[1,2-g]-1,2-dihydroquinoline derivatives which bind to retinoid receptors and have retinoid-like, retinoid antagonist or retinoid inverse agonist-like biological activity. More specifically, the present invention relates to a synthetic process for preparing certain benzo[1,2-g]-chrom-3-ene, benzo[1,2-g]-thiochrom-3-ene and benzo[1,2-g]-1,2-dihydroquinoline derivatives which are described in U.S. Pat. No. 5,728,846 and which bind to retinoid receptors and primarily have retinoid antagonist or retinoid inverse agonist-like biological activity.
2. Background Art
U.S. Pat. No. 5,728,846 discloses substituted benzo[1,2-g]-chrom-3-ene, benzo[1,2-g]-thiochrom-3-ene and benzo[1,2-g]-1,2-dihydroquinoline derivatives which bind to retinoid receptors and have retinoid-like, retinoid antagonist or retinoid inverse agonist-like biological activity. Other examples of compounds having retinoid-like biological activity and condensed tricyclic or dihydronaphthalene structure are found in the following U.S. and foreign patent disclosures: U.S. Pat. Nos. 5,523,457; 5,559,248; 5,648,514; 5,877,207, WO 94/14777 and EPO 0 661-259 A1.
The publication Dawson and William H. Okamura, Chemistry and Biology of Synthetic Retinoids, published by CRC Press Inc., 1990, pages 334-335, 354 and 324-356 is of special interest as an overview of the chemistry and biology of retinoid-like compounds.
Among the compounds disclosed in U.S. Pat. No. 5,728,846, benzo[1,2-g]-chrom-3-ene derivatives, and particularly 4-[2,2-dialkyl-4-(aryl, heteroaryl or alkyl)-6,7-benzochrom-3-en-7-yl]benzoic acids or benzoic acid esters are of particular interest primarily as retinoid antagonist and/or retinoid inverse agonist compounds. Whereas U.S. Pat. No. 5,728,846 discloses synthetic processes for the preparation of these compounds, the present invention describes a different and significantly improved synthetic process for the preparation of this class of compounds.